상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

Benproperine, an ARPC2 inhibitor, suppresses cancer cell migration and tumor metastasis

 

ARPC2 저해제인 벤프로페린의 암 전이 효과

Authors 

Yae Jin YoonYoung-Min HanJiyeon ChoiYu Jin LeeJieun YunSu-Kyung LeeChang Woo LeeJong Soon KangSeung-Wook ChiJeong Hee MoonSangku LeeDong Cho HanByoung-Mog Kwon

Publisher 

Elsevier

Issue Date 

2019

Citation 

Biochemical Pharmacology

Keywords 

ARPC2Arp2/3 complexBenproperineDrug repurposingMetastasis

Abstract 

Metastasis is the leading cause of cancer mortality and cancer cell migration is an essential stage of metastasis. We identified benproperine (Benp, a clinically used antitussive drug) as an inhibitor of cancer cell migration and an anti-metastatic agent. Benp selectively inhibited cancer cell migration and invasion, which also suppressed metastasis of cancer cells in animal models. Actin-related protein 2/3 complex subunit 2 (ARPC2) was identified as a molecular target of Benp by affinity column chromatography with Benp-tagged Sepharose beads. Benp bound directly to ARPC2 in cells, which was validated by pull-down assay using Benp-biotin and label-free biochemical methods such as the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA). Benp inhibited Arp2/3 function, showing disruption of lamellipodial structure and inhibition of actin polymerization. Unlike Arp2/3 inhibitors, Benp selectively inhibited the migration of cancer cells but not normal cells. ARPC2-knockdown cancer cells showed defective cell migration and suppressed metastasis in an animal model. Therefore, ARPC2 is a potential target for anti-metastatic therapy, and Benp has the clinical potential to block metastasis. Furthermore, Benp is a useful agent for studying the functions of the Arp2/3 complex in cancer cell migration and metastasis.

URI 

https://doi.org/10.1016/j.bcp.2019.01.017

ISSN 

0006-2952

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)